This application outlines plans for continued development of informatics tools for 3D structural and protein localization data from the cellular and subcellular domains, in the structural range of 1 nm3 to 10 pm3. This scale encompasses macromolecular complexes, organelles, multi-component structures like synapses and cellular structures such as spiny dendrites. These structures represent the heart of information processing in the nervous system and provide a bridge between the molecular information being assembled at one end of the biological continuum and the large-scale brain mapping being performed at the other. During the previous funding period, a web-accessible database, the Cell Centered Database or CCDB, was developed specifically for housing this type of high-resolution data. During this same period, we developed a novel approach for linking resources like the CCDB to other independent databases containing data taken at different scales or in different disciplines. The current application outlines plans for further expanding CCDB functionality, developing tools for situating its data into a larger spatial context using specially-developed brain atlas tools and promoting interoperability with other cell level databases. We will accomplish the following specific aims: (1) Extend CCDB by adding a wider variety of data, (2) Provide mechanisms to represent, explore and query cellular data at multiple spatial resolutions, (3) Develop techniques and tools to represent, query, compare and analyze expression patterns of proteins at different spatial scales and (4) Extend the knowledge-based mediation technique to scale up to a larger variety of interoperating sources. Development will take place in the context of core research on the structure of cells in the cerebella cortex, a highly ordered cytoarchitectural region, and the neostriatum, an area of exceeding neurochemical complexity with little cytoarchitectural differentiation. Detailed structural models will be built of the principle cells in these areas, detailing the distributions of key macromolecules like glutamate and dopamine receptors, which will serve as the basis for developing cell-level atlases for integrating properties at the level of the single cell. Although we focus on these two key brain areas, the resulting informatics tools wit1 be extensible to other challenging and clinically important areas of the nervous system, such as the hypothalamus and chemically coded nuclei. ? ?
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